The elucidation of the unique mechanisms of pathogenicity and infectivity of prions requires experiments in animal models. The objective of the Animal Core is to support the animal experiment needs of the Program efficiently and in a standardized, uniform and coordinated fashion. In the long term, the Animal Core will provide animal models to facilitate future advances in prion research. The Animal Core will provide the following services: 1) The Animal Core will breed and maintain mice. Genetic background, genetic variants, housing conditions and procedures will be standardized and uniform. 2) The Animal Core will design, acquire, characterize, breed and maintain new transgenic lines and breed to generate mice with desired combinations of genetic variants. 3) The Animal Core will inoculate, monitor and record the status and symptoms of animals (mice and hamsters), and will prepare and provide tissues to the projects and the Neuropathology Core. 4) The Animal Core will maintain the database recording animal experiment data to coordinate with the other Cores and Research Projects. Uniformity of animal experiments will be ensured through careful design and characterization of new transgenics, standardization of genetic backgrounds, quality control of genotyping, standardized procedures and common personnel and active oversight. The Animal Core serves all three Research Projects to a similar degree. It does not duplicate any existing resources at institutions participating in this Program Project. Project Summary/